Moulitsas was born in Chicago, Illinois, to a Salvadoran mother and a Greek father. He moved with his family to El Salvador in 1976, but later returned to the Chicago area in 1980 after his family fled threats placed on their lives by communist insurgents during the Salvadoran Civil War.[2] As an adult, he has recounted his memories of the civil war, including an incident that occurred when he was 8 years old, in which he saw communist guerrillas murdering students who had been accused of collaborating with the government.[4]

After leaving the army, he attended Northern Illinois University and graduated in 1996 with two bachelor degrees, majoring in philosophy, journalism, and political science.[7][8] While attending NIU, he wrote for the college newspaper, the Northern Star and became its editor-in-chief in 1995. As a writer, he questioned NIU's policy of spending student fee money on athletic programs, generating a negative response from school officials, and also waged an unsuccessful campaign to save the school's journalism program. In 2007, he was inducted into the Northern Star Hall of Fame, an honor bestowed by the newspaper's alumni association.[7] After graduating from NIU, he attended the Boston University School of Law from 1996 to 1999, earning a J.D. degree.[8]

Moulitsas describes himself as a recovering Catholic, and says that while he has many problems with the Church, Salvadoran martyr and archbishop Oscar Romero is still his greatest hero and inspiration.[9]

After graduating from law school, Moulitsas moved to the San Francisco Bay Area, where he worked as a project manager at a web development shop. He founded Daily Kos in May 2002, and has managed the blog as a full-time occupation since early 2004.[2]

In April 2004, Moulitsas and Daily Kos became the focus of controversy over a statement that he posted in the comments section of a blog post about Blackwater USA employees who were killed and mutilated in Fallujah:

"Let the people see what war is like. This isn't an Xbox game. There are real repercussions to Bush's folly. That said, I feel nothing over the death of merceneries [sic]. They aren't in Iraq because of orders, or because they are there trying to help the people make Iraq a better place. They are there to wage war for profit. Screw them."[20]

In a blog post the next day, Moulitsas defended and clarified his remarks:

"My language was harsh, and, in reality, not true. Fact is, I did feel something. That's why I was so angry.

I was angry that five soldiers—the real heroes in my mind—were killed the same day and got far lower billing in the newscasts. I was angry that 51 American soldiers paid the ultimate price for Bush's folly in Iraq in March alone. I was angry that these mercenaries make more in a day than our brave men and women in uniform make in an entire month. I was angry that the US is funding private armies, paying them $30,000 per soldier, per month, while the Bush administration tries to cut our soldiers' hazard pay.[21] I was angry that these mercenaries would leave their wives and children behind to enter a war zone on their own violition [sic].

On March 17, 2008, Moulitsas stated that Senator Hillary Clinton, who was then involved in a protracted race against Senator Barack Obama for the Democratic presidential nomination, "doesn't deserve fairness on this site" because she "fails the test of the guiding principles of this site" and because Clinton had "no reasonable chance of victory". He accused her of "formenting civil war in order to overturn the will of the Democratic electorate" and said Clinton's "only path to victory [...] is via coup by super delegate."[22] His statement was precipitated by a "strike" conducted by several pro-Clinton diarists, even though none of these posters were paid or in any way officially linked to the site.[23] Moulitsas responded directly to the "strike" by saying that it was more like a "boycott", noting that "It's a big Internet, so I hope they find what they're looking for."[24]

In addition to political pursuits, Moulitsas co-founded SB Nation, a network of sports blogs, with Tyler Bleszinski (of Athletics Nation) in 2003.[34] The network now covers all major American leagues (MLB, NBA, NFL, and NHL), as well as dozens of colleges and other specific sports like golf, cycling, and ultimate fighting.[35] In 2011, SB Nation became Vox Media and began expanding, raising capital to acquire and develop other blog networks.[36]